Background: Thrombocytopenia is a known adverse event (AE) of givinostat, an oral histone deacetylase inhibitor indicated for the treatment of Duchenne muscular dystrophy (DMD).
Objectives: To further characterize thrombocytopenia with givinostat treatment using data from the phase 3 EPIDYS trial (NCT02851797).
Methods: A total of 179 boys aged ≥6 years with DMD were assigned to oral givinostat (n=118) or placebo (n=61) over 18 months, while continuing systemic corticosteroids. The preferred AE terms of “thrombocytopenia” and “platelet count decreased” were assessed.
Results: Overall, 38 (32.2%) givinostat-treated patients experienced thrombocytopenia or decreased platelet count (AE terms aggregated) compared with 0 patients receiving placebo. All AEs of thrombocytopenia/decreased platelet count were grade 1 or 2 in severity, and none resulted in study drug withdrawal. A total of 17 (14.4%) and 16 (13.6%) givinostat-treated patients required dose reduction owing to thrombocytopenia or decreased platelet count, respectively. No events of thrombocytopenia or decreased platelet count led to temporary treatment interruption. The median (interquartile range [IQR]) time to platelet count nadir (first minimum value post baseline) with givinostat was 85.0 (41.0–254.0) days. The median (IQR) time to platelet count recovery (time from the minimum value < lower limit of normal [n=62] to the first value within normal limits) was 26.0 (12.0–43.0) days. Conclusions: With givinostat treatment, platelet count reductions occur early, and levels recover to normal within 1 month. Although thrombocytopenia/decreased platelet count resulted in dose reductions in 17 (14.4%) and 16 (13.6%) givinostat-treated patients, respectively, all events were mild or moderate in severity and managed without treatment interruption.